The mechanism of iron-mediated myocardial injury by reactive oxygen metabolites will be studied in cultured cardiac myocytes, isolated rabbit hearts and intact dogs. Cultured myocytes will be exposed to oxygen metabolites or activated neutrophils and the time course of membrane injury (determined by leakage of enzymes or radiolabeled chromium), production of hydroxyl radical (detected by spin trapping), and appearance of myocardial lipid peroxides (by direct measurement) will be determined. The effect of reduced iron availability through iron chelation, alterations in intracellular pH or downregulation of transferrin receptors on myocardial injury will be studied. The efficacy of highly permeable scavengers of reactive oxygen metabolites, membrane protective agents, and infusion of a sulfhydryl donor in preventing myocardial injury, inhibiting lipid peroxidation, and avoiding depletion of sulfhydryl groups will be examined in cultured myocytes, isolated hearts or intact canine models exposed to potential oxidant injury.